Computational and Rational Design of Single-Chain Antibody against Tick-Borne Encephalitis Virus for Modifying Its Specificity.

Ivan K Baykov,Olga M Kurchenko,Nina V Tikunova,Pavel Y Desyukevich,Ekaterina E Mikhaylova

doi:10.3390/v13081494

Abstract

Tick-borne encephalitis virus (TBEV) causes 5−7 thousand cases of human meningitis and encephalitis annually. The neutralizing and protective antibody ch14D5 is a potential therapeutic agent. This antibody exhibits a high affinity for binding with the D3 domain of the glycoprotein E of the Far Eastern subtype of the virus, but a lower affinity for the D3 domains of the Siberian and European subtypes. In this study, a 2.2-fold increase in the affinity of single-chain antibody sc14D5 to D3 proteins of the Siberian and European subtypes of the virus was achieved using rational design and computational modeling. This improvement can be further enhanced in the case of the bivalent binding of the full-length chimeric antibody containing the identified mutation.

Highlights

Tick-borne encephalitis virus (TBEV) belongs to tick-transmitted flaviviruses and causes severe arboviral infection in Europe and northeastern Asia [1]
In 2019, more than 3200 cases were officially confirmed in European countries according to the European Centre for Disease Prevention and Control (ECDC) report [2], and approximately 1500 cases were registered in Russia [3]
The Siberian and European subtypes are considered less pathogenic than the Far Eastern subtype, both mild and severe cases of TBE are associated with infection by any of the subtypes [1,9]

Summary

Introduction

Tick-borne encephalitis virus (TBEV) belongs to tick-transmitted flaviviruses and causes severe arboviral infection in Europe and northeastern Asia [1]. There are three major subtypes of TBEV, namely, the Far Eastern, Siberian, and European subtypes, each of which differs in terms of severity of the disease [1]. The mortality caused by the virus depends on the subtype and ranges from 1–2% for the European subtype to 5–20% for the Far Eastern subtype [6]. The Siberian and European subtypes are considered less pathogenic than the Far Eastern subtype, both mild and severe cases of TBE are associated with infection by any of the subtypes [1,9]. All three major subtypes of TBEV require control and prevention

Methods

Results

Conclusion